NUCLEOTIDE METABOLISM &PROMOTION OF CARCINOGENESIS

Project Details

Description

The objective of the research program is to establish the extent
to which dietary modification can result in a nucleotide imbalance
which might result in the misincorporation of uracil into DNA and
thereby initiate or promote carcinogenesis. Increased synthesis of
pyrimidine ribonucleotides and decreased synthesis of purine
ribonucleotides has been observed in rat liver on a diet high in
orotate or deficient in arginine. The tissue specificity of this
effect is being studied in rats and mice. The extent to which
deoxyribonucleotide levels are changed will be investigated with
particular emphasis on the metabolism of dUTP. Dietary
influence on the activity of hydrolases for dUTP and on uracil-
DNA glycosylase will be examined to determine if there is an
adaptive response in these enzymes. The influence of a high
orotate diet and an arginine-deficient diet on the
misincorporation of uracil into DNA and the appearance of strand
breaks during excision repair will be investigated. The studies
should throw some light on the question of whether a high orotate
diet is promotional for hepatocarcinogenesis through formation of
lipid oxidation products or through creation of a nucleotide
imbalance.
StatusFinished
Effective start/end date1/1/901/31/92

Funding

  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute

ASJC

  • Oncology
  • Cancer Research

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